TransKingAmyloid

Signalosomes are high-order molecular machines involved in activation and execution of programmed cell death in immunity. Termed apoptosomes/inflammasomes in mammals and resistosomes in plants, their assembly can be driven by the aggregation of amyloids in large suprastructures. We recently uncovered such signalosomes in bacteria and hypothesized their assembly into amyloid-based suprastructures. This proposal aims at providing for the first time the basic molecular understanding of the regulation of cell death by bacterial amyloid-based signalosomes. It combines structural biology (solid-state and solution NMR, crystallography and lipid-protein interaction) with in vivo analysis of signalosome assembly in bacteria and a fungal system. These mechanisms will allow for a comprehensive direct comparison of evolutionarily related signaling amyloid motifs in humans, fungi and bacteria.